Objective: The serotonergic system is implicated in the pathophysiology
of obsessive-compulsive disorder (OCD). However, the distinct role of
serotonin (5-HT) receptor subtypes remains unclear. This study
investigates the contribution of 5-HT2A and 5-HT2C receptors in the
modulation of persistence in the reinforced spatial alternation model of
OCD.
Methods: Male Wistar rats were assessed for spontaneous and
pharmacologically induced (by m-chlorophenylpiperazine: mCPP)
directional persistence in the reinforced alternation OCD model.
Systemic administration of mCPP (non-specific 5-HT agonist, 2.5 mg/kg),
M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084
(selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used.
Experiment 1 investigated M100907 and SB242084 effects in animals
spontaneously exhibiting high and low persistence during the early
stages of alternation training. Experiment 2 investigated M100900 and
SB242084 effects on mCPP-induced persistence.
Results: Under the regime used in Experiment 1, 5-HT2A or 5-HT2C
receptor antagonism did not affect spontaneous directional persistence
in either high or low persistence groups. In Experiment 2, 5-HT2C but
not 5-HT2A receptor antagonism significantly reduced, but did not
abolish, mCPP-induced directional persistence.
Conclusions: These findings suggest that 5-HT2C but not 5-HT2A receptors
contribute to the modulation of mCPP-induced persistent behaviour,
raising the possibility that the use of 5-HT2C antagonists may have a
therapeutic value in OCD. (C) 2013 Elsevier B.V. All rights reserved
